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Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome

Leukemia volume 18, pages 693–702 (2004)Cite this article

Abstract

Additional chromosomal aberrations occur frequently in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) of childhood. The treatment outcome of these patients is heterogeneous. This study assessed whether such clinical heterogeneity could be partially explained by the presence and characteristics of additional chromosomal abnormalities. Cytogenetic descriptions were available for 249 of 326 children with Ph+ ALL, diagnosed and treated by 10 different study groups/large single institutions from 1986 to 1996. Secondary aberrations were present in 61% of the cases. Chromosomes 9, 22, 7, 14, and 8 were most frequently abnormal. Most (93%) karyotypes were unbalanced. Three main cytogenetic subgroups were identified: no secondary aberrations, gain of a second Ph and/or >50 chromosomes, or loss of chromosome 7, 7p, and/or 9p, while other secondary aberrations were grouped as combinations of gain and loss or others. Of the three main cytogenetic subgroups, the loss group had the worst event-free survival (P=0.124) and disease-free survival (P=0.013). However, statistical significance was not maintained when adjusted for other prognostic factors and treatment. Karyotypic analysis is valuable in subsets of patients identified by molecular screening, to assess the role of additional chromosomal abnormalities and their correlation with clinical heterogeneity, with possible therapeutic implications.

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Acknowledgements

We thank the many cytogeneticists who contributed cases for this study, as well as the clinicians who participated in the studies. A special thanks to the children and their parents, who made this study possible.

Author information

Authors and Affiliations

  1. Department of Pathology, The Ohio State University, Columbus, OH

    N A Heerema

  2. USA

    N A Heerema

  3. Department of Hematology and Oncology, Oncogenetic Laboratory, Giessen, Germany

    J Harbott

  4. Department of Clinical Medicine, Prevention and Biotechnology, Section of Medical Statistics, University of Milano-Bicocca, Italy

    S Galimberti & M G Valsecchi

  5. Midwest Children's Cancer Center, Milwaukee, WI, USA

    B M Camitta

  6. Childrens Center for Cancer & Blood Diseases, Childrens Hospital, Los Angeles, CA, USA

    P S Gaynon

  7. Department of Hematology & Oncology, Children's University Hospital, Hamburg, Germany

    G Janka-Schaub

  8. Department of Pediatrics, University Hospital Groningen, Groningen, The Netherlands

    W Kamps

  9. Laboratorio di Oncoematologia Dipartimento di Pediatria, Universita di Padova, Padua, Italy

    G Basso & V Conter

  10. St Jude Children's Research Hospital and University of Tennessee Health Sciences Center, Memphis, TN, USA

    C-H Pui & S C Raimondi

  11. Pediatric Hematology & Oncology, MHH Children's Hospital, Hannover, Germany

    M Schrappe & H Riehm

  12. Hopital Saint Louis, Paris, France

    M-F Auclerc

  13. University of Alabama at Birmingham, Birmingham, AL, USA

    A J Carroll

  14. Cancer Sciences Division, Cytogenetics Group, University of Southampton, UK

    C J Harrison

  15. University of Mississippi Medical Center, Jackson, MS, USA

    J Pullen

  16. Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, UK

    S Richards

  17. Children's Oncology Group, Arcadia, CA, USA

    H N Sather

  18. Department of Statistics, Children's Oncology Group Research Data Center and University of Florida, Gainesville, FL, USA

    J J Shuster

  19. Dana-Farber Cancer Institute and Children's Hospital, Boston, MA, USA

    L B Silverman

  20. Onco-Ematologia Pediatrica, Ospedale dei Bambini, G Di Cristina, Palermo, Italy

    M Aricò

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Consortia

for the Acute Lymphoblastic Leukemia Study Groups: ALL-BFM and CoALL (Germany), AIEOP (Italy), DCLSG (Netherlands), FRALLE (France), CCG, DFCI, POG and St Jude (USA), and UKALL (UK)

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Correspondence to N A Heerema.

Additional information

Supported in part by CA-21765 from the National Cancer Institute, the Associazione Italiana Ricerca Cancre, a Center of Excellence Grant for the State of Tennessee and the American Lebanese Syrian Associated Charities (ALSAC). C-H Pui is the American Cancer Society-FM Kirby Clinical Research Professor

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Heerema, N., Harbott, J., Galimberti, S. et al. Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome. Leukemia 18, 693–702 (2004). https://doi.org/10.1038/sj.leu.2403324

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